title: Evaluation of CD86/CD28 and CD40/CD154 pathways in regulating monocyte-derived CD80 expression during their interaction with allogeneic endothelium.
abstract: This study was designed to examine the role of monocyte-derived CD80 in providing costimulation to CD4+ cells, and to determine whether monocyte-derived CD80 expression is regulated by CD86/CD28 and CD40/CD154 pathways during allogeneic immunoresponses. Human endothelial cells (EC) and purified monocytes cocultured with or without CD4+ cells were analyzed by real-time quantitative polymerase chain reaction (RT-PCR) and florescence-activated cell scanning (FACS). Peripheral blood mononuclear cells (PBMC)-EC cocultures with or without costimulation blockade were analyzed by FACS. The effects of CD154 and CD28 blockade to inhibit lymphocyte proliferation were evaluated by mixed lymphocyte-EC reaction (MLER). RT-PCR demonstrated upregulation of CD80 transcripts in EC-stimulated monocytes in the absence of CD4+ cells. However, the surface expression of CD80 was undetectable. The expression of CD80 was restored in the presence of CD4+ cells. Additionally, CD80 blockade partially inhibited CD4+ cell proliferation induced by EC-conditioned monocytes. Monocytes demonstrated upregulation of CD80 on the surface during PBMC-EC interaction. CD86, CD28, and CD154 blockade did not prevent upregulation of monocyte-derived CD80 expression. CD28 and CD154 blockade partially inhibited lymphocyte proliferation of MLER. In summary, EC-stimulated monocytes upregulated CD80 expression at the transcript level but not on their surface in the absence of T cells. The surface expression of monocyte-derived CD80 is upregulated on EC-stimulated monocytes in the presence of T cells. CD154/CD40 and CD28/CD86 blockade cannot prevent monocyte-derived CD80 expression, suggesting that CD80 upregulation is through a CD154- or CD86-independent pathway. Specific therapy to prevent monocyte activation may be required for successful allograft transplantation.
authors.affiliation: Department of Transplantation, Jinan City Central Hospital, P.R. China.
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.forename: C
authors.initials: C
authors.lastname: Wu
authors.forename: B
authors.initials: B
authors.lastname: Zhu
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Xu
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001011:Aorta / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics*; D051940:B7-2 Antigen / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D019013:CD40 Antigens; D023201:CD40 Ligand